Overview of technical solutions and assessment of clinical usefulness of capsule endoscopy

The paper presents an overview of endoscopic capsules with particular emphasis on technical aspects. It indicates common problems in capsule endoscopy such as: (1) limited wireless communication (2) the use of capsule endoscopy in the case of partial patency of the gastrointestinal tract, (3) limited imaging area, (4) external capsule control limitations. It also presents the prospects of capsule endoscopy, the most recent technical solutions for biopsy and the mobility of the capsule in the gastrointestinal tract. The paper shows the possibilities of increasing clinical usefulness of capsule endoscopy resulting from technological limitations. Attention has also been paid to the current role of capsule endoscopy in screening tests and the limitations of its effectiveness. The paper includes the author's recommendations concerning the direction of further research and the possibility of enhancing the scope of capsule endoscop

New Techniques in Gastrointestinal Endoscopy

As result of progress, endoscopy has became more complex, using more sophisticated devices and has claimed a special form. In this moment, the gastroenterologist performing endoscopy has to be an expert in macroscopic view of the lesions in the gut, with good skills for using standard endoscopes, with good experience in ultrasound (for performing endoscopic ultrasound), with pathology experience for confocal examination. It is compulsory to get experience and to have patience and attention for the follow-up of thousands of images transmitted during capsule endoscopy or to have knowledge in physics necessary for autofluorescence imaging endoscopy. Therefore, the idea of an endoscopist has changed. Examinations mentioned need a special formation, a superior level of instruction, accessible to those who have already gained enough experience in basic diagnostic endoscopy. This is the reason for what these new issues of endoscopy are presented in this book of New techniques in Gastrointestinal Endoscopy

An Investigation of the Diagnostic Potential of Autofluorescence Lifetime Spectroscopy and Imaging for Label-Free Contrast of Disease

The work presented in this thesis aimed to study the application of fluorescence lifetime spectroscopy (FLS) and fluorescence lifetime imaging microscopy (FLIM) to investigate their potential for diagnostic contrast of diseased tissue with a particular emphasis on autofluorescence (AF) measurements of gastrointestinal (GI) disease. Initially, an ex vivo study utilising confocal FLIM was undertaken with 420 nm excitation to characterise the fluorescence lifetime (FL) images obtained from 71 GI samples from 35 patients. A significant decrease in FL was observed between normal colon and polyps (p = 0.024), and normal colon and inflammatory bowel disease (IBD) (p = 0.015). Confocal FLIM was also performed on 23 bladder samples. A longer, although not significant, FL for cancer was observed, in paired specimens (n = 5) instilled with a photosensitizer. The first in vivo study was a clinical investigation of skin cancer using a fibre-optic FL spectrofluorometer and involved the interrogation of 27 lesions from 25 patients. A significant decrease in the FL of basal cell carcinomas compared to healthy tissue was observed (p = 0.002) with 445 nm excitation. A novel clinically viable FLS fibre-optic probe was then applied ex vivo to measure 60 samples collected from 23 patients. In a paired analysis of neoplastic polyps and normal colon obtained from the same region of the colon in the same patient (n = 12), a significant decrease in FL was observed (p = 0.021) with 435 nm excitation. In contrast, with 375 nm excitation, the mean FL of IBD specimens (n = 4) was found to be longer than that of normal tissue, although not statistically significant. Finally, the FLS system was applied in vivo in 17 patients, with initial data indicating that 435 nm excitation results in AF lifetimes that are broadly consistent with ex vivo studies, although no diagnostically significant differences were observed in the signals obtained in vivo.Open Acces

Automated detection of celiac disease on duodenal biopsy slides: a deep learning approach

Celiac disease prevalence and diagnosis have increased substantially in recent years. The current gold standard for celiac disease confirmation is visual examination of duodenal mucosal biopsies. An accurate computer-aided biopsy analysis system using deep learning can help pathologists diagnose celiac disease more efficiently. In this study, we trained a deep learning model to detect celiac disease on duodenal biopsy images. Our model uses a state-of-the-art residual convolutional neural network to evaluate patches of duodenal tissue and then aggregates those predictions for whole-slide classification. We tested the model on an independent set of 212 images and evaluated its classification results against reference standards established by pathologists. Our model identified celiac disease, normal tissue, and nonspecific duodenitis with accuracies of 95.3%, 91.0%, and 89.2%, respectively. The area under the receiver operating characteristic curve was greater than 0.95 for all classes. We have developed an automated biopsy analysis system that achieves high performance in detecting celiac disease on biopsy slides. Our system can highlight areas of interest and provide preliminary classification of duodenal biopsies prior to review by pathologists. This technology has great potential for improving the accuracy and efficiency of celiac disease diagnosis.Comment: Accepted in Journal of Pathology Informatic

Assessment and Diagnosis of Human Colorectal and Ovarian Cancer using Optical Imaging and Computer-aided Diagnosis

Tissue optical scattering has recently emerged as an important diagnosis parameter associated with early tumor development and progression. To characterize the differences between benign and malignant colorectal tissues, we have created an automated optical scattering coefficient mapping algorithm using an optical coherence tomography (OCT) system. A novel feature called the angular spectrum index quantifies the scattering coefficient distribution. In addition to scattering, subsurface morphological changes are also associated with the development of colorectal cancer. We have observed a specific mucosa structure indicating normal human colorectal tissue, and have developed a real-time pattern recognition neural network to localize this specific structure in OCT images, enabling classification of the morphological changes associated with the progression of human colon cancer. Differentiating normal from malignant tissues is critically important, however, identifying different subtypes of abnormalities is also useful in clinical diagnosis. We have designed a feature extraction method using texture features and computer-vision related features to characterize different types of colorectal tissues. We first ranked these features according to their importance, then trained two classifiers: one for normal vs. abnormal, and the other one for cancer vs. polyp, where polyp is a pre-cancer marker. In assessing tissue abnormalities, optical absorption reveals contrast related to tumor microvasculature and tumor angiogenesis. Spatial frequency domain imaging (SFDI), a powerful wide field, label-free imaging modality, is sensitive to both absorption and scattering. We designed a computer-aided diagnostic algorithm, AdaBoost, to use multispectral SFDI imaging for ex vivo assessment of different types of colorectal tissues, including normal and cancerous tissue and adenomatous polyps. For diagnosis of human ovarian cancer, we first designed a histogram-based feature extraction algorithm. Then we trained and tested traditional machine learning methods utilizing these histogram features for ovarian cancer diagnosis. We also explored the use of these features in characterizing human fallopian tubes, which are believed to be the origin of the most lethal subtype of human ovarian cancers

Länsimainen ruokavalio ja peritty syöpäalttius paksusuolen syövän riskitekijöinä

Lifestyle and diet have a major effect on the development of colorectal cancer (CRC). Dietary habits of Western populations in particular are recognized as a risk factor for CRC. However, the mechanisms that mediate the effects of Western-style diet (WD) on colorectal tumor development are largely unknown. CRC develops via multiple steps which involve genetic changes, such as mutations in growth-regulatory genes, and epigenetic alterations, such as CpG island hypermethylation. Lynch syndrome (LS) is one of the most common inherited cancer susceptibility syndromes. It is caused by inherited defects of the DNA mismatch repair genes (MMR), which together with other genetic and epigenetic changes are known to accelerate tumorigenesis. MMR defects are known to accelerate tumor progression in LS but the early events leading to polyp formation and the timing and order of the molecular hits remain unknown. A long-term feeding experiment with mouse models for LS and sporadic CRC was conducted to characterize tumor-promoting changes in normal colonic mucosa caused by WD and/or genetic predisposition. Changes in the proteome of histologically normal colonic mucosa were monitored at different time points of feeding experiment (5 weeks, 12, 18 and 21 months) with two high-throughput proteomic methods followed by analysis of affected pathways. Data from proteomic analysis indicated that the proteome was more consistently changed by diet and aging than by genotype. Overall, 21 out of 26 colonic tumors were detected in mice fed with WD. Proteomic analysis indicated disrupted lipid metabolism and increased oxidative stress in the normal-appearing tissue in association with WD. Moreover, proteome analyses revealed increased cell proliferation and decreased apoptotic processes in the normal colon mucosa of mice fed with WD, which may promote colorectal tumorigenesis. Finally, proteomic data coupled with measurement of bile acids in tissue specimens indicated that WD induces downregulation of intracellular bile acid transport, resulting in disrupted bile acid homeostasis which may provide a possible mechanism underlying the tumor-promoting effects of the diet. Studies on sporadic CRC have demonstrated that promoter hypermethylation leading to gene silencing can act as an alternative mechanism to mutations in early stages of tumor development but its importance in hereditary CRC remains unknown. We analyzed tissue specimens gathered during colonoscopy surveillances and colectomies performed on human LS mutation carriers to define changes in CpG island methylation that occur at different stages of the tumor progression sequence. Methylation changes at different stages of tumor progression were analyzed in relation to MMR gene expression, and normal tissue biopsies were studied for carcinogenic fields . In addition, we aimed to clarify the role of CpG island hypermethylator phenotype (CIMP) in the LS-associated tumorigenesis. Results indicate that the expression of the MMR protein corresponding to the gene mutated in the germline decreases along with dysplasia but occurs as a relatively late event in the tumor progression sequence, suggesting the presence of other somatic events that drive neoplastic transformation. Indeed, significant increase in the average degree of methylation of two candidate genes (SFRP1 and SLC5A8) was observed in normal colonic mucosa biopsies from patients with CRC (high-risk mucosa) when compared to those without (low-risk mucosa), indicating a possible carcinogenic field. Moreover, methylation was found to increase in LS adenomas and carcinomas along with dysplasia. These findings emphasize the importance and early appearance of epigenetic alterations in LS-associated tumorigenesis. In summary, the results offer new insights into the initiating molecular mechanisms through which Western-style diet and DNA methylation contribute to hereditary and sporadic colorectal carcinogenesis.Syövän kehittymiseen vaikuttavat perimän ohella monet elintapoihin liittyvät tekijät kuten ravitsemus ja liikunta. Paljon energiaa, tyydyttyneitä rasvoja ja punaista lihaa sekä vähän kuituja, D-vitamiinia, kalsiumia ja folaattia sisältävän länsimaisen ruokavalion (WD, Western diet) on todettu altistavan paksusuolen syövälle. Syövän kehittyminen on seurausta monien geneettisten ja epigeneettisten muutosten kasautumisesta solun perimään. Geneettisellä muutoksella tarkoitetaan geenin emäsjärjestyksen rakenteellista mutaatiota, kun taas epigeneettinen muutos vaikuttaa geenien toiminnan säätelyyn DNA:n emäsjärjestyksen pysyessä ennallaan. Monet solun ulkopuoliset tekijät, kuten ravintoaineet, voivat vaikuttaa epigeneettiseen säätelyyn aktivoiden ja passivoiden geenejä. Nämä muutokset kasautuvat solujen perimään ja voivat olla syöpää estäviä tai syövälle altistavia. Geenisäätelyyn vaikuttavia epigeneettisiä muutoksia tapahtuu suolen epiteelisoluissa jo hyvin varhaisessa syövän kehitysvaiheessa ennen varsinaisen esiasteen muodostumista. Väitöskirjatutkimuksessa selvitettiin, miten länsimainen ruokavalio yhdessä tai ilman perittyä syöpäalttiutta muuttaa paksusuolen limakalvon geenien toimintaa ja miten nämä muutokset lisäävät syöpäriskiä. Ensimmäisessä ja toisessa osatyössä tutkittiin paksusuolen normaalilimakalvon proteiini-ilmentymien profiilia perinnöllisen suolistosyövän hiirimallia hyödyntäen. Suurin osa paksusuolen kasvaimista havaittiin länsimaista ruokavaliota mallintavissa ryhmissä. Tutkimuksissa havaittiin merkittäviä muutoksia paksusuolen limakalvon proteiini-ilmentymien profiilissa länsimaista ravintoa mallintavan dieettiryhmän ja verrokkiryhmän välillä. Muutokset viittasivat solujakautumisen lisääntymiseen limakalvolla, rasva- ja sappihappoaineenvaihdunnan häiriöihin sekä happiradikaalien kasaantumiseen limakalvon soluihin WD-dieettiryhmässä. Geenisäätelyyn vaikuttavaa DNA:n metyloitumista tiedetään tapahtuvan suolen limakalvolla jo hyvin varhaisessa syövän kehitysvaiheessa. Ruokavalion tiedetään olevan ikääntymisen ohella yksi tärkeä DNA:n metyloitumiseen vaikuttava tekijä. Osassa paksusuolisyöpäkasvaimia havaitaan yksittäisten geenien hypermetyloitumista, osassa taas useiden geenien samanaikaista säätelyalueiden hypermetylaatiota, jota kutsutan CIMP-ilmiöksi (CpG island hypermethylator phenotype). Kolmannessa osatyössä syöpäalttiuteen liittyviä DNA:n metylaatiomuutoksia tutkittiin perinnölliselle paksusuolensyövälle altistuneiden mutaationkantajien (Lynchin oireyhtymä) paksusuolen tähystyksissä otetuista limakalvonäytteistä, esiasteista ja karsinoomista. Näytteet tutkimusta varten kerättiin 2011 2013 yhteistyössä seurantatähystyksistä vastaavien kirurgien kanssa. Tutkimuksessa havaittiin metylaation lisääntymistä esiasteissa ja karsinoomissa. Jo varhaisissa esiasteissa todettiin paksusuolen syöpäkasvaimille tyypillistä CIMP-ilmiötä. Yli 50 vuotta vanhoilla henkilöillä, joilla oli diagnosoitu paksusuolen syöpä, lisääntynyt metylaatio näkyi myös normaalilimakalvolla. Syöpäriskiä lisäävien varhaisten geenimuunnosten tunnistaminen ja havaitseminen ajoissa mahdollistaisi syövän ennaltaehkäisyn ja parantaisi riskin arviointia

Detection and classification of gastrointestinal cancer and other pathologies through quantitative analysis of optical coherence tomography data and goniophotometry

The changes in light interaction between healthy and diseased tissues have been investigated as a potential diagnostic application. Here we attempt to differentiate between healthy and pathological gastrointestinal tissues using quantitative analysis of optical coherence tomography (OCT) data and goniophotometry. A goniophotometer was constructed and calibrated using titanium oxide and microsphere phantoms. Measurements were carried out on human gastrointestinal tissue sections collected using the methodology described below. The anisotropy factor g was extracted from the scattering curves by fitting the Henyey-Greenstein function. Measurements on human samples were in the forward scattering range with g 0.6-0.7, in agreement with the literature. Optical coherence tomography imaging was carried out on gastrointestinal tissues collected from patients undergoing elective surgery or endoscopy at St. Mary’s Hospital, London. In total 146 patients were included. Data was processed using gradient analysis of signal attenuation and morphological analysis with kNN classification. Results were correlated with histological diagnoses. Gradient analysis results were statistically significant across most categories, showing particularly good differences in the gradient distributions between healthy and diseased oesophageal tissues. Morphological analysis and kNN classification produced sensitivity and specificity values for healthy oesophagus and cancer in surgical specimens reaching 100% / 97.87% and 99.99% / 99.91% respectively and high accuracy in detecting Barrett's oesophagus in endoscopic specimens, with sensitivity and specificity values of 99.80% and 99.02%. Results in rectal tissue where also noteworthy, with detection of dysplasia reaching a sensitivity and specificity of 99.55% / 96.01%. Despite limitations in our work, we have shown that the detection of gastrointestinal pathologies using quantitative analysis of OCT data is a promising technique with good ex vivo results. Transferring the methodology to the in vivo domain holds a lot of potential as a future quick and reliable diagnostic technique.Open Acces